The overall aim of the proposed projects is to develop, refine, and make available to the neuroscientific community a body of computer software for rigorously based simulation of the behavior of neuronal systems. The programs embody a compartmental description of neuronal morphology and include such mechanisms as voltage-dependent ion channels, kinetics of calcium-ion binding by a number of substrates, mobilization and packaging of neurotransmitter in vesicles, calcium-triggered release of transmitter quanta into the synaptic cleft, receptors for neurotransmitter that produce time- and voltage-dependent conductance changes or a time-varying concentration of second messenger, and modulation of ion channels by calcium ion or by second messenger. Available manipulations include steady or time-varying current injection, deterministic or stochastic stimulation of axons, single- or dual- electrode voltage clamps, and intracellular injection of calcium ion. Among the variables that can be recorded and plotted are membrane potentials, individual ionic and synaptic currents, individual and summed conductances, calcium-ion concentrations, free and bound neurotransmitter, and receptor states. The programs will be interactive and will make extensive use of high-resolution color graphics. They will enable neurobiologists to organize data collection and will provide theoretical frameworks for testing hypotheses and comparing prediction with experiment. Use of such models enriches the information obtained from animal experiments and eventually will make possible more explicit and quantitative determination of therapeutic neuropharmacological regimes.